Reaction of aziridinecar☐ylic acids with thiols in aqueous solution. the formation of β-amino acid

Abstract

Enantiomers of 3-methyl-2-aziridinecar☐ylic acids (1-d and 1-l) and 2-aziridinecar☐ylic acids (2-d and 2-l) reacted easily with thiophenol, cysteine and glutathione in aqueous solution or in sodium phosphate buffer solution at room temperature and gave predominantly β-amino acid derivatives with sulfur substituents at their α-position. From 1-d and thiophenol, (2 S, 3 R)-3-amino-2-phenylthiobutanoic acid (3-d) was produced predominantly. In order to confirm the structure, 3-d was converted to (3 S, 4 R)-3-phenylthio-4-methylazetidin-2-one (5) using the Ohno reaction. The configurations of 3-d and 6 were determined by X-ray diffraction and 13C NMR spectrum analysis, respectively. We concluded that the ring-opening reaction of unactivated aziridinecar☐yhc acids with thiols in aqueous solution occurred predominantly on C-2 of the aziridine ring with inversion of the configuration at this position. The reaction offers a good route for stereoselective synthesis of peptides or β-lactam derivatives.